The administration of vitamin A to pregnant mice produces facial and limb malformations which resemble some of those observed in humans. The purpose of this project is to determine the cellular and biochemical mechanism by which vitamin A causes malformations. The results indicate that the vitamin A induced malformations are based on the inhibition of neural crest cell migration and the inhibition of chondrogenesis. Further studies, using developing limb bud cell cultures, showed that vitamin A inhibits the synthesis of cartilage type proteoglycans and stimulates the mannosylation of glycoproteins. Vitamin A also causes contact inhibition and increased cell-cell adhesion suggesting cell surface changes. BIBLIOGRAPHIC REFERENCES: Hand, A.R. and Hassell, J.R.: Tissue fixation with diimidoesters as an alternative to aldehydes. II. Cytochemical and biochemical studies of rat liver fixed with dimethyl suberimidate. J. Histochem. and Cytochem. 24: 1001-1011, 1976. Hassell, J.R. and Pratt, R.M.: Elevated levels of cAMP alters the effect of epidermal growth factor in vitro on programmed cell death in the secondary palatal epithelium. Exp. Cell Res. 106: 55-62, 1977.